Lisofylline analogs and methods for use

Abstract

Analogs of a Lisofylline (LSF), and synthetic methods for the preparation of such analogs are provided. The analogs of LSF provided have the ability to protect cell viability, particularly the ability to protect pancreatic β-cells.

1 . A compound having formula III: 
     
       
         
         
             
             
         
       
       where each R 3  is independently hydrogen, C 1-22 alkyl, C 2-22 alkenyl or C 2-22  alkynyl, provided that at least one R 3  group is not hydrogen, or a pharmaceutically acceptable salt thereof. 
     
   
   
       2 . The compound of  claim 1 , wherein each R 3  independently is hydrogen, ethyl, butyl, hexyl, octyl, decyl, dodecyl, hexadecyl, 2-methyl-hexyl, 3-methyl-hexyl, 4-methyl-octyl, 5-ethyl-octyl, 5-phenyl-octyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, or 3-hexynyl. 
   
   
       3 . The compound of  claim 2 , wherein each R 3  independently is hydrogen, ethyl, butyl, hexyl, octyl, decyl, dodecyl, or hexadecyl. 
   
   
       4 . The compound of  claim 3 , wherein each R 3  independently is hydrogen, ethyl, butyl, hexyl, or octyl. 
   
   
       5 . The compound of  claim 1 , having the formula: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       or pharmaceutically acceptable salts thereof. 
     
   
   
       6 . A pharmaceutical composition comprising a compound of  claim 1 , in combination with a pharmaceutically acceptable carrier. 
   
   
       7 . A method for preventing or treating a pathological condition or symptom in a mammal, wherein the protection of β-cells from Th1 cytokine-induced dysfunction or the onset of Type 1 diabetes can be reduced, and such activity is desired, comprising administering to said mammal an effective amount of a compound of  claim 1 , or pharmaceutically acceptable salt thereof. 
   
   
       8 . The method of  claim 7 , wherein the pathological condition or symptom is Type 1 diabetes. 
   
   
       9 . The method of  claim 7 , wherein the mammal is a human. 
   
   
       10 . A method for preventing or treating a pathological condition or symptom in a mammal, wherein the protection of pancreatic β-cells is desired comprising contacting the cells with an effective protective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
   
   
       11 . The method of  claim 10 , wherein the mammal is a human. 
   
   
       12 . A method for preventing or treating a pathological condition or symptom in a mammal wherein treatment of an inflammatory and autoimmune condition is desired comprising administering to said mammal an effective amount of a compound of  claim 1 , or pharmaceutically acceptable salt thereof. 
   
   
       13 . The method of  claim 12 , wherein the inflammatory or autoimmune condition is atherosclerosis, type 2 diabetes, disorders associated with visceral obesity, multiple sclerosis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, or Alzheimer's disease. 
   
   
       14 . The method of  claim 13 , wherein the mammal is a human. 
   
   
       15 - 22 . (canceled) 
   
   
       23 . The pharmaceutical composition of  claim 6 , comprising a liquid carrier. 
   
   
       24 . The pharmaceutical composition of  claim 6 , comprising solid carrier.